Due to the rapidly increasing number of therapeutic humanized monoclonal antibodies being developed and FDA-approved, there is a clear need for improved cell line development to support recombinant therapeutic protein manufacturing. There is a current and projected shortage of worldwide GMP manufacturing capacity for these therapeutic proteins, and approaches for getting more protein from the available bioreactor capacity are deemed critical. Generation of stable high-secreting producer cell lines is a major bottleneck, requiring a 4-10 month process with no guarantee of success. Cloning of cells for high expression of a secreted product (e.g., antibody) is a particular challenge because the secreted product does not remain associated with the cell. The novel laser-enabled analysis and processing (LEAP(tm)) technology platform for high-throughput cell imaging and in situ laser-mediated cell manipulation has been used to develop the Cell Xpress(tm) application to address these market needs. Phase I results demonstrate significantly improved specific antibody secretion rates from LEAP-derived clones, along with an acceleration of the process, as compared to current methods. The goal of Phase II is to build upon Phase I success by pursuing the following specific aims: (1) expand Cell Xpress utility to an additional cell line and therapeutic (non-antibody) protein; (2) extend Cell Xpress into labor-intensive downstream operations; (3) apply Cell Xpress to bioprocess optimization and monitoring; and (4) automate and integrate the Cell Xpress process. Phase II success will result in an automated and broadened Cell Xpress application with large, near-term market potential for biopharmaceutical cell line development as both a commercial fee-for- service and product application on LEAP. In biopharmaceutical manufacturing, over $40 billion worth of therapeutic proteins are produced annually from large-scale culture of recombinant cell lines producing a secreted protein. The number of biopharmaceuticals in clinical development and being FDA approved each year is growing dramatically, resulting in a worldwide shortage of GMP manufacturing capacity for these proteins. Therefore, methods to improve cell line development, the yield of protein within the current bioreactor capacity constraints, and overall cost and efficiency of these processes are highly desirable. [unreadable] [unreadable]